New insights into the pathogenesis of bladder exstrophy-epispadias complex.
J Pediatr Urol
; 9(6 Pt B): 996-1005, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-23743131
Bladder exstrophy-epispadias complex (BEEC) is a complex and debilitating congenital disease. Familial and twin studies suggest a possible genetic component in BEEC pathogenesis. Bladder mesenchyme (detrusor) development requires induction by a signal from bladder urothelium, and we and others have shown the Shh-Gli-Bmp4 signalling pathway is likely to be involved. P63 is a master regulator in epithelial stratification and is expressed in urothelium. We have shown that p63 knock-out mice undergo excessive urothelial apoptosis. Failure of mesenchymal induction by epithelium leads to BEEC. We further demonstrated that insertion/deletion (in/del) polymorphisms (1 base pair (bp) ins and 4 bp ins., and 12 bp del) in the ΔNP63 promoter reduce transcriptional efficiency, and are associated with a statistically significant increase in the risk of BEEC in humans. Furthermore, a Genome-Wide Expression Profiling (GWEP) study suggests possible involvement of PERP in human BEEC. Intriguingly, PERP is a direct target of p63 during development, and is also involved in epithelial stratification. PERP co-localizes with desmosome, and both PERP and desmosome are essential for maintaining tissue integrity by cellular adhesion and epithelial stratification. A recent study showed that PERP and desmosome expression levels are abnormal in human BEEC patients. This review describes the role of the P63 > PERP > desmosome pathway in the development of human bladder during embryogenesis. We hypothesize that disruption of this pathway may increase the risk of BEEC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Extrofia de la Vejiga
/
Epispadias
/
Regulación del Desarrollo de la Expresión Génica
/
Desmosomas
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Pediatr Urol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Reino Unido